The rabbit MHC locus, designated RLA, encodes class I and class II molecules similar to those encoded in the human and marine systems. However, recent structural data on the MHC of the rabbit suggest that the RLA is considerably closer to that of man than to that of mouse. Protein structural and molecular genetic studies of the rabbit RLA genes have been conducted using a rabbit T -cell line, RL-5. The rabbit class I family contains only between 8 to 13 genes, as opposed to 18 and 36 in man and mouse respectively. Structural and sequencing data are now available for four cDNAs and three corresponding genes. One of them, 19-1, has been shown to encode the only class I protein expressed at the surface of the cells. Using probes derived from these genes, expression studies at the mRNA level have been performed using rabbit cells and normal rabbit tissues. The genes 19-1 and 5-2 are ubiquitously expressed. However, the third gene, 7-1, is transcribed only in T -cell lines and lymphoid tissue containing T-cells. Transection experiments of the 7-1 gene to determine if 7-1 has the same specific pattern of expression in other cellular environments. The differential pattern of expression of the rabbit class I genes provide a useful system to study the mechanisms involved in the regulation of expression of these genes. Search for sequences and factors involved in the expression of the gene 19-1 are in progress by using CAT assays with the promoter region of this gene. DNA regions controlling the up regulation of the rabbit class I by several cytokines are also under investigation. Studies of the rabbit class II genes revealed that there are rabbit genes corresponding to every human class II genes found in the HLA-D region. Rabbit class II genes corresponding to the HLA -DR, -DP, -DQ, and DZ alpha genes have been partially or fully sequenced. Genetic analysis based on RFLP using selected probes from class I and II genes have provided molecular data covering linkage of class I and class II subregions in RLA and new haplotypes were found in the typing and extended family.